Systemic Therapy Options for Moderate to Severe Atopic Dermatitis

Since the approval of dupilumab in 2017, the landscape of targeted therapies for the treatment of moderate to severe atopic dermatitis (AD) has widened. The evolution of AD treatment, case studies, and best clinical practices were discussed in a recent Dermatology Times® Around the Practice® series titled “Atopic Dermatitis First-Line Treatment Options: Systemic Therapies for Moderate to Severe Atopic Dermatitis.”¹

From left to right: Panelists Andrew Blauvelt, MD, MBA; Jonathan Silverberg, MD, PhD, MPH; Lisa Swanson, MD; and Brad Glick, DO, MPH, FAOCD.

The panelists, who have been long-time practitioners, acknowledged the impressive advances in AD treatments, especially in the last decade. “I do believe in the era that we’re in, there is a greater understanding of the need and the use of injectables subcutaneously,” said Brad Glick, DO, MPH, FAOCD, board-certified dermatologist and dermatologic surgeon at Glick Skin Institute in Margate and Wellington, Florida. “It’s not that we just started them a year ago or 2 years ago. This is a more than 20-year wave.”

Lisa Swanson, MD, who practices at Ada West Dermatology in Boise, Idaho, emphasized how the variety of AD treatment options is impressive. When Swanson participates in speaking engagements, she always touches base with new dermatologists to share the progression of treatment options. “I’ll always ask [groups] if there is anyone in the room who has been practicing for less than 6 years. If there is, I’ll tell them, ‘You don’t know how much we struggled trying to manage bad AD.’… It’s so much more rewarding to be able to help people, and it’s been a game changer for our patients and their families. It’s really been a wonderful time to be in practice,” she shared.

The panel agreed with Swanson’s testament to it being a rewarding time in AD treatment—especially with the availability of systemic agents, new nonsteroidal topicals, and other methods to treat patients collaboratively.

Treatment Options

One of the challenges mentioned by Jonathan Silverberg, MD, PhD, MPH, a professor at George Washington University in Washington, DC, is the number of options available in treatment. “For some [patients], speed is going to be super important. For some, it’s going to be safety first. For some, it’s going to be oral vs injectable [treatment]. You highlight all options at the beginning. Lay them all out. Give them the landscape, and let them decide based on what works for them,” he said.

His colleagues shared their approach to treatment selection.

“I break it down when I’m talking with patients about either biologics, to include dupilumab and tralokinumab depending on age, or Janus kinase (JAK) inhibitors, to include abrocitinib and upadacitinibas long as they’re aged 12 and up. I lay out the pros and cons of each and let the patient decide,” Swanson explained.

Andrew Blauvelt, MD, MBA, an investigator at the Oregon Medical Research Center in Portland, Oregon, has run a small private dermatology practice for years. Since he has conducted mostly clinical trials, he opened up the conversation to biologics vs JAK inhibitors, which he has extensively researched. “There were 2-plus years where we have had open trials for tralokinumab and/or lebrikizumab, and abrocitinib and upadacitinib at the same time. I’d do what we do in practice—I’ve done it for 3 or 4 years—going through the pros and cons of each class and then [listening to] what they say,” he explained. “It’s been fascinating...having these conversations, but in the context of clinical trial choice, it’s been about half and half [from patients and physicians].”

Short- Vs Long-Term Treatments

Speed can sometimes become the determining factor in choosing an AD treatment plan.

“With atopic dermatitis, even compared with psoriasis, it’s crucially important. These patients are super itchy, and they can’t sleep at night. The faster the better,” Glick said. “That’s my approach, and that’s one reason why I like the JAK inhibitors. We haven’t talked about this, but the topical agent that has been put into our toolbox is also quite effective. When we’re talking about this, we’re able to cover that mild to moderate sphere by having a topical and then 2 new oral JAKs.”

The panel went on to suggest what they call better alternatives, such as a 2-, 4-, or 6-week dose of a JAK inhibitor to cool off patients instead of 2 weeks of prednisone.

Blauvelt shared his work on the JADE REGIMEN trial² (NCT03627767), which treats study participants with a high dose of abrocitinib for the first 3 months. Data from the study is helping expand insight on episodic therapy. One-third of responders were kept on the high dose, while one-third were dropped to a lower dose. The remaining one-third went to no treatment. “Yes, most patients recurred off-drug, but not all of them. About 20% did not recur out to 1 year. The patients who did the best were staying on the high dose, but half the patients on the lower dose did well.… In a trial, we haven’t had anything better to help us with episodic treatment,” he said.

“What about the new cyclosporine?” Glick asked the panel. “That’s something we can intervene with that’s much likely safer.”

“That’s a great point,” Silverberg acknowledged. “The one limitation the cyclosporine always had was the 1-year recommendation from the FDA, not to go beyond that. We’re reluctant. If we can, we keep them on it not more than6 months. The drug survival for cyclosporine is terrible. The advantage of the JAKs is dual because you have the ability to go up to a higher dose for rescue, but we also don’t want to ignore the long-term treatment goals. We’ve got data up to 52 weeks for the different JAK inhibitors. The field has worked hard over the past decades, before I even got into the field, to establish the importance of long-term treatment. Dose flexibility is an important feature that allows you to attack both the acute aspects and the chronic.”

Blauvelt also points out that tralokinumab and the up-and-coming lebrikizumab may be better options for some patients than dupilumab since there is less of a risk of conjunctivitis.

Age-Specific Trends

Before delving into AD cases, the panel briefly acknowledged trends among pediatric and adolescent patients. Swanson said that in her patient population, for kids and teenagers, she is always going to place the first primary emphasis on safety and tend to choose dupilumab over an oral JAK to prioritize safety rather than rapid onset. Not everyone shared Swanson’s experience, though.

“Fifty-fifty holds true for my teenager studies. It’s not so much shot vs pill,” Blauvelt shared. “So much happens in the life of a teenager and what they’re doing now vs 3 months from now: new significant other, new sports, new things in school. The speed is particularly important in teens because of so many life-changing events. One of my patients had a hard time playing soccer because he would get so bad from being on the grass of a soccer field. He’s a soccer star now, and his life changed a lot after dupilumab.”

Silverberg pointed out another common life event requiring strategic treatment: weddings. “We’ll have the bride-to-be coming in 2 weeks before her wedding saying, ‘I can’t look like this for my wedding,’ ” he explained. “When you need that speed, there’s a subset of patients on dupilumab and tralokinumab who can get that rapid response, but you can’t predict that easily.”

Case Study

Blauvelt, Glick, Swanson, and Silverberg were presented with a pediatric AD case and discussed their approaches to treating the patient.

A 6-year-old boy previously diagnosed with moderate AD was referred to a dermatologist with red, dry, itchy patches covering his neck and arms. Previous treatment was with nonpharmacological products (emollients and moisturizers) and multiple topical corticosteroids. His parents noted that the rashes and itching have been getting worse for the past year. When talking with dermatologists, his parents mentioned disturbed sleep causing him to routinely miss preschool. His parents admitted to sometimes dressing him in long-sleeved clothes even on hot days to prevent his peers and family from seeing scratches on his arms.

Swanson first acknowledged the impact of sleep on young patients, and their families losing sleep too. Building on that point, Glick said that itch management is a top priority to help eliminate those sleepless nights. “Sometimes we have challenges and maybe try some other things, like antihistamines that don’t always work great, but sometimes those sedative effects [may] help at nighttime,”he said.

In this patient case, Swanson said she would grade it as moderate AD and first present classic options consisting of a topical steroid for flares and a nonsteroid for maintenance. She would also share a compounded product used a lot in pediatric dermatology called the Aron regimen, which is a compounded mix of 30 gof betamethasone valerate, 0.1%, 24 gof mupirocin, and 400 gof either vanicream or plastibase in a 1-lb tub. She describes it as 8/9 moisturizer and said it works well for young children but not older patients. It can be used up to5 times a day for flare-ups or once before bedtime for prevention and maintenance. “It’s appealing to families who are even a little bit fearful of topical steroids because it’s so incredibly dilute. This particular patient is also in the age range for dupilumab, which is worth considering with the impact of his itch,” she told the panel.

“I give them a little burst of corticosteroids. It could be something as potent as betamethasone valerate for a couple of weeks, and then I’ll cycle in one of the topical calcium urine inhibitors.… And dare I say this because we’ve had some reasonable success with it, but we do have a topical PDE-4 inhibitor in crisaborole, [which is] approved down to the age of 3 months,” Glick added.

Looking Ahead

Blauvelt offered perspective as a clinical trial investigator. Oftentimes he sees patients who have only been offered topical steroids their entire lives. He emphasized how vital it is to use all of the treatment options in the dermatology armamentarium because the patients he works with are hoping a clinical trial drug can providelong-term relief.

Swanson and Silverberg both expressed their excitement to utilize topical roflumilast, currently approved for patients with psoriasis, to bring relief to patients with AD too. They believe it will be appealing to pediatric patients and their parents. Silverberg also addressed how social media can play a role in determining which treatment patients and their families are willing toadhere to.

“I think the insurance companies will have their own say in this, but most parents, after they go on social media, they’re scared of topical steroids. I think we all agree, it’s probably overblown most of the time, but you don’t want to waste 20 minutes in clinic either talking them down [or] they’re never really fully confident in the therapy. Which means they’re not going to give it a fair shake,” Silverberg explained. “I’d rather give them something—and even let’s say with…crisaborole, even if comparative efficacy-wise, it might be less effective than a betamethasone—[that they will] actually use because they’re not scared of it. Sometimes they’ll get better results because they’re putting it on. So I think it’s an important option. You’ve got to know your patients too. Not everyone’s going to be able to be adherent with all the topicals.”

Top Discussion Takeaways

Overall, the panel of experts highlighted the importance of being aware of the AD treatment options for all ages and knowledgeable about what is in the pipeline to enhance those options. When evaluating treatment plans for patients, it is crucial to inquire about symptoms such as itch severity, treatment priorities, and desired timelines, and to ask the right questions to ensure the treatment option prescribed is adhered to by the patient and their family.

References

1. Silverberg J, Swanson E, Blauvelt A, Glick B. Atopic dermatitis first line treatment options: Systemic therapies for moderate-to-severe AD. Dermatology Times. May 9, 2023. Accessed May 18, 2023. https://www.dermatologytimes.com/around-the-practice/atopic-dermatitis-first-line-treatment-options-systemic-therapies-for-moderate-to-severe-ad
2. Blauvelt A, Silverberg JI, Lynde CW, et al. Abrocitinib induction, randomized withdrawal, and retreatment in patients with moderate-to-severe atopic dermatitis: Results from the JAK1 atopic dermatitis efficacy and safety (JADE) REGIMEN phase 3 trial. Journal of the American Academy of Dermatology. 2022;86(1):104-112. doi:10.1016/j.jaad.2021.05.075